Is COL2A1 p.Pro952Thr (c.2854C>A) pathogenic?

COL2A1 p.Pro952Thr (c.2854C>A) is classified Benign/Likely benign in COL2A1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0518); Rare (popmax 0.546%, eas); Associated with type 2 collagenopathy.

What condition is associated with COL2A1 p.Pro952Thr (c.2854C>A)?

COL2A1 p.Pro952Thr (c.2854C>A) is associated with type 2 collagenopathy, Stickler syndrome type 1 (ClinVar).

How common is COL2A1 p.Pro952Thr (c.2854C>A) in the general population?

COL2A1 p.Pro952Thr (c.2854C>A) is rare (popmax 0.546%, eas) (gnomAD).

What do computational predictors say about COL2A1 p.Pro952Thr (c.2854C>A)?

AlphaMissense predicts likely benign (score 0.0518) — an in-silico prediction, not a clinical call.

COL2A1 p.Pro952Thr

c.2854C>A · rs140740708 · VCV751462

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0518 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.546%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

type 2 collagenopathy

Computational evidence

Protein change
AlphaMissense	0.0518	likely benign
REVEL	0.362	indeterminate
SaProt	LLR -8.65	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.65	GERP -3.8, phastCons 0.094
Regional constraint	o/e 0.62	unconstrained · MANE · 21 kb · p 2.4e-45 · regional, not allelic
Overall
CADD	13.14	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.546% East Asian · 245/44,882 alleles

Filtering AF 0.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.468%

Overall 0.0205% 330/1,613,548 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.546%	183
South Asian	0.0626%	1,598
Remaining individualsnot grpmax-eligible	0.0384%	2,604
Admixed American	0.00167%	60,012
European (non-Finnish)	0.000254%	393,334

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: COL2A1
Protein: p.Pro952Thr
Coding: c.2854C>A
MANE Select: NM_001844
dbSNP: rs140740708
Type: single nucleotide variant
Location: chr12:47978638 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 11 PDB
Residue 952: the 'disordered' region; the 'triple-helical region' region

Full COL2A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

type 2 collagenopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Stickler syndrome type 1

Similar variants

COL2A1 c.1222-2A>G Pathogenic ★★ same condition
COL2A1 c.1365+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL2A1 c.1420-2A>G Pathogenic/Likely pathogenic ★★ same condition
COL2A1 c.1527+135G>A Pathogenic/Likely pathogenic ★★ same condition
COL2A1 c.1581+1G>A Likely pathogenic ★★ same condition
COL2A1 c.1833+1G>A Pathogenic ★★ same condition
COL2A1 c.1887+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL2A1 c.1888-2A>C Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/col2a1-p-pro952thr (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown